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28.10.2019 | Article

miR-409-3p is reduced in plasma and islet immune infiltrates of NOD diabetic mice and is differentially expressed in people with type 1 diabetes

verfasst von: Giuliana Ventriglia, Francesca Mancarella, Guido Sebastiani, Dana P. Cook, Roberto Mallone, Chantal Mathieu, Conny Gysemans, Francesco Dotta

Erschienen in: Diabetologia | Ausgabe 1/2020

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Abstract

Aims/hypothesis

MicroRNAs (miRNAs) are a novel class of potential biomarkers emerging in many diseases, including type 1 diabetes. Here, we aim to analyse a panel of circulating miRNAs in non-obese diabetic (NOD) mice and individuals with type 1 diabetes.

Methods

We adopted standardised methodologies for extracting miRNAs from small sample volumes to evaluate a profiling panel of mature miRNAs in paired plasma and laser-captured microdissected immune-infiltrated islets of recently diabetic and normoglycaemic NOD mice. Moreover, we validated the findings during disease progression and remission after anti-CD3 therapy in NOD mice, as well as in individuals with type 1 diabetes.

Results

Plasma levels of five miRNAs were downregulated in diabetic vs normoglycaemic mice. Of those, miR-409-3p was also downregulated in situ in the immune islet infiltrates of diabetic mice, suggesting an association with disease pathogenesis. Target-prediction tools linked miR-409-3p to immune- and metabolism-related signalling molecules. In situ miR-409-3p expression correlated with insulitis severity, and CD8⁺ central memory T cells were found to be enriched in miR-409-3p. Plasma miR-409-3p levels gradually decreased during diabetes development and improved with disease remission after anti-CD3 antibody therapy. Finally, plasma miR-409-3p levels were lower in people recently diagnosed with type 1 diabetes compared with a non-diabetic control group, and levels were inversely correlated with HbA_1c levels.

Conclusions/interpretation

We propose that miR-409-3p may represent a new circulating biomarker of islet inflammation and type 1 diabetes severity.

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Titel: miR-409-3p is reduced in plasma and islet immune infiltrates of NOD diabetic mice and is differentially expressed in people with type 1 diabetes
verfasst von: Giuliana Ventriglia
Francesca Mancarella
Guido Sebastiani
Dana P. Cook
Roberto Mallone
Chantal Mathieu
Conny Gysemans
Francesco Dotta
Publikationsdatum: 28.10.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 1/2020
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-019-05026-1

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